Project Summary/Abstract Idiopathic pulmonary fibrosis (IPF) is the most common idiopathic interstitial lung disease (ILD), with an estimated 3-year survival rate of 50% As we previously reported, 6-9% of smokers have interstitial lung abnormalities (ILA) on CT scans. These abnormalities are associated with reduced lung volumes, greater symptoms and exercise impairments, and an increased risk of death. Additional work in the Framingham Heart Study further demonstrated a strong correlation between ILA and polymorphisms in the promoter region of the MUC5B gene. This polymorphism has been strongly linked to the development of interstitial pulmonary fibrosis (IPF). The aggregate of our data suggest that ILA is a clinically relevant CT feature and that a subset of these subjects likely progress to more fulminant interstitial lung disease (ILD) or IPF. Defining new prognostic markers of ILA progression are critical to better determine the patients at a higher risk of ending on a fatal disease course like IPF. The availability over the last year of new effective therapies for IPF makes even more important the need of earlier disease identification where therapeutic attenuation of functional decline will be more impactful than at the latter end stages of established IPF. Our proposal addresses the discovery of ILA presence on CT imaging by means of the delineation of different parenchymal subtypes by patterns in the regional CT attenuation and its distribution throughout the chest. We propose to look at changes of fibrotic tissue within ILA regions to determine the prognostic value of baseline textural CT features for the identification of subjects at greatest risk for the development of IPF. We will test and validate those models in 2000 subjects of the COPDGene cohort with baseline and follow-up information.